Trials / Recruiting

RecruitingNCT05711615

Testing Low-Dose Common Chemotherapy (Liposomal Doxorubicin) in Combination With an Anti-Cancer Drug, Peposertib, in Advanced Sarcoma

A Phase 1 Study of Peposertib (M3814) and Low-Dose Liposomal Doxorubicin in Patients With Metastatic Leiomyosarcoma and Other Soft Tissue Sarcomas

Status: Recruiting
Phase: Phase 1
Study type: Interventional
Enrollment: 30 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of combination therapy with liposomal doxorubicin and peposertib in treating patients with sarcoma that has spread from where it first started, to other places in the body (metastatic), or cannot be removed by surgery (unresectable) and for which no known cure is available (advanced). Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Liposomal doxorubicin is a form of the anticancer drug doxorubicin that is contained inside very tiny, fat-like particles. Liposomal doxorubicin may have fewer side effects and work better than other forms of the drug. Peposertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also enhance the activity of chemo- and radiotherapy. There is some pre-clinical evidence in animal models that combining peposertib with liposomal doxorubicin can shrink or stabilize certain types of cancer for longer than either drug alone, but it is not known if this will happen in people. Combination therapy with liposomal doxorubicin and peposertib may be effective in treating patients with advanced sarcoma.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of peposertib in combination with low-dose pegylated liposomal doxorubicin hydrochloride (liposomal doxorubicin) as evaluated by the dose-limiting toxicity (DLT) rate at each tested dose level. (Dose Escalation) II. To determine the recommended phase 2 dose (RP2D) of liposomal doxorubicin and peposertib combination and determine the maximal tolerated dose (MTD) if identified. (Dose Escalation) III. To obtain a more precise determination of adverse events (e.g. dose limiting toxicities estimate at the selected dose). (Dose Expansion) SECONDARY OBJECTIVES: I. To assess the pharmacokinetics of peposertib and liposomal doxorubicin used in combination with each other. (Dose Escalation) II. To estimate the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in patients with leiomyosarcoma treated with peposertib and low-dose liposomal doxorubicin. (Dose Expansion) III. To estimate the progression free survival (PFS) in patients with leiomyosarcoma treated with peposertib and low-dose liposomal doxorubicin. (Dose Expansion) IV. To assess the pharmacokinetics of peposertib and liposomal doxorubicin used in combination with each other. (Dose Expansion) V. To assess whether DNA damage is exaggerated by the low-dose liposomal doxorubicin in combination with peposertib in patients with homologous recombination (HR)-deficiency. (Dose Expansion) CORRELATIVE OBJECTIVES: I. To test the hypothesis that soft tissue sarcomas (STS) with homologous recombination deficiency (HRD) like leiomyosarcomas (LMS) will be more susceptible to DNA-protein kinase inhibitor (PKi) in combination with low-dose liposomal doxorubicin. II. To test the hypothesis that gammaH2AX and pNBS1 can be used as pharmacodynamic biomarkers of response to DNA-PKi in combination with low-dose liposomal doxorubicin. III. To test the hypothesis that disease activity correlates with circulating tumor DNA levels in the plasma. OUTLINE: This is a dose-escalation study of peposertib and liposomal doxorubicin followed by a dose-expansion study. Patients receive peposertib orally (PO) twice daily (BID) on days 1-28 of each cycle and liposomal doxorubicin intravenously (IV) on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression, unacceptable toxicity or withdrawal of consent. Patients undergo blood sample collection and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial. Patients also undergo tissue biopsy and echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening and on the trial. Patients are followed for 30 days after removal from study or until death, whichever occurs first.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo tissue biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT scan
PROCEDURE	Echocardiography Test	Undergo ECHO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
DRUG	Pegylated Liposomal Doxorubicin Hydrochloride	Given IV
DRUG	Peposertib	Given PO

Timeline

Start date: 2024-02-06
Primary completion: 2026-05-03
Completion: 2026-05-03
First posted: 2023-02-03
Last updated: 2026-04-13

Locations

16 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT05711615. Inclusion in this directory is not an endorsement.